Analysis of proteome alterations induced by sAPPalpha treatment of mouse primary neurons.

• Applicant: Dr. Daniela Hartl, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 183345740

Soluble APP alpha (sAPPα), a cleavage product of the amyloid precursor protein (APP), is known to have neurotrophic functions. It has been proposed to counteract the neurotoxic effects of Aß, which is another cleavage product of APP and plays a key role in Alzheimer disease (AD). sAPPα is present at lower levels in brains of AD patients which suggests that its loss may be detrimental in AD. Although a number of studies already exist, the mechanisms of sAPPα action in the brain are far from being understood. Therefore, analyzing the biological functions of sAPPα is very important for AD research as well as for the understanding of molecular mechanisms of normal brain function. In the project proposed here, I will analyze the effects of sAPPα administration on the proteome of primary mouse cortical neurons. Using our well established proteomics approach (large-gel 2-D electrophoresis and mass spectrometry) as well as the technique of isotope coded protein labeling (ICPL) I will screen for sAPPα dependent protein alterations. These data will provide the foundation to develop important new insights of how secreted sAPPα acts on its target cells on a molecular level. In addition, by applying sAPPα to neurons lacking APP, I will investigate the hypothesis that APP might act as cell-surface receptor for its own cleavage product sAPPα.

• DFG Programme: Research Grants